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利用一种新型的捕获循环肿瘤细胞的体内设备对肺癌患者的肿瘤细胞进行计数和分子特征分析。

Enumeration and Molecular Characterization of Tumor Cells in Lung Cancer Patients Using a Novel In Vivo Device for Capturing Circulating Tumor Cells.

机构信息

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Department of Pneumology, University Clinic Ulm, Ulm, Germany.

出版信息

Clin Cancer Res. 2016 May 1;22(9):2197-206. doi: 10.1158/1078-0432.CCR-15-1416. Epub 2015 Dec 14.

DOI:10.1158/1078-0432.CCR-15-1416
PMID:26667488
Abstract

PURPOSE

The use of circulating tumor cells (CTC) as "liquid biopsy" is limited by the very low yield of CTCs available for subsequent analyses. Most in vitro approaches rely on small sample volumes (5-10 mL).

EXPERIMENTAL DESIGN

Here, we used a novel approach, the GILUPI CellCollector, which enables an in vivo isolation of CTCs from peripheral blood. In total, 50 lung cancer patients were screened in two subsequent device applications before and after therapy (n = 185 applications).

RESULTS

By in vivo isolation, 58% (108/185) of the patients were positive for ≥1 CTC (median, 5 CTCs; range, 1-56 cells) as compared with 27% (23/84; range, 1-300 cells) using the FDA-cleared CellSearch system. Furthermore, we could show that treatment response during therapy was associated with significant decreases in CTC counts (P = 0.001). By dPCR, mutations in the KRAS and EGFR genes relevant for treatment decisions could be detected in CTCs captured by in vivo isolation and confirmed in the primary tumors of the same patients.

CONCLUSIONS

In vivo isolation of CTCs overcomes blood volume limitations of other approaches, which might help to implement CTC-based "liquid biopsies" into clinical decision making. Clin Cancer Res; 22(9); 2197-206. ©2015 AACR.

摘要

目的

循环肿瘤细胞(CTC)作为“液体活检”的应用受到可用于后续分析的 CTC 产量非常低的限制。大多数体外方法依赖于小样本量(5-10mL)。

实验设计

在这里,我们使用了一种新的方法,即 GILUPI CellCollector,它可以从外周血中进行体内 CTC 分离。总共对 50 名肺癌患者进行了两次设备应用(n=185 次应用)前后的筛选。

结果

与使用美国 FDA 批准的 CellSearch 系统相比,通过体内分离,58%(108/185)的患者至少有 1 个 CTC 呈阳性(中位数,5 个 CTC;范围,1-56 个细胞),而该系统的阳性率为 27%(23/84;范围,1-300 个细胞)。此外,我们还表明,治疗期间的治疗反应与 CTC 计数的显著下降相关(P=0.001)。通过 dPCR,可以在体内分离捕获的 CTC 中检测到与治疗决策相关的 KRAS 和 EGFR 基因突变,并在同一患者的原发性肿瘤中得到证实。

结论

CTC 的体内分离克服了其他方法的血液体积限制,这可能有助于将基于 CTC 的“液体活检”纳入临床决策。临床癌症研究;22(9);2197-206。©2015AACR。

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